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Inherited prion disease with six octapeptide repeat insertional mutation—molecular analysis of phenotypic heterogeneity by Simon Mead, Mark Poulter, Jon.

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Presentation on theme: "Inherited prion disease with six octapeptide repeat insertional mutation—molecular analysis of phenotypic heterogeneity by Simon Mead, Mark Poulter, Jon."— Presentation transcript:

1 Inherited prion disease with six octapeptide repeat insertional mutation—molecular analysis of phenotypic heterogeneity by Simon Mead, Mark Poulter, Jon Beck, Thomas E. F. Webb, Tracy A. Campbell, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Jonathan D. F. Wadsworth, Andrew King, Peter Lantos, and John Collinge Brain Volume 129(9):2297-2317 August 21, 2006 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

2 Linked microsatellite haplotypes on chromosome 20. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

3 The UK 6-OPRI prion disease pedigree The smaller pedigree 2 shares the same microsatellite and SNP haplotype background as the larger pedigree. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

4 (A) Cumulative age of onset and age at death curves; (B) cumulative age of onset curves for the two genotypes at codon 129. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

5 (A) Age at onset and (B) age at death histograms with curves modelling the data assuming a normal distribution. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

6 Of historical interest is an autopsy report of an individual in the pedigree (III.5) who was admitted in 1897 and died in 1901. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

7 MRI appearances of 6-OPRI prion disease These show cerebral and cerebellar atrophy (A) Coronal T1 at the level of the hippocampus, (B) Axial T2 at the level of the basal ganglia and (C) Sagittal T1 (all from patient VII.20). Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

8 Neuropathology from two autopsy cases of 6-OPRI prion disease. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

9 Pearson correlation of age of onset versus duration of disease. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

10 Kaplan–Meier survival curves. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

11 Molecular PrPSc typing in 6-OPRI prion disease (A) Immunoblot with anti-PrP monoclonal antibody 3F4. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

12 Heritability of age of onset. Simon Mead et al. Brain 2006;129:2297-2317 © The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org


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